RELT：一种与肾透明细胞癌进展和免疫调控相关的预后生物标志物

RELT: A Prognostic Biomarker Associated with Renal Clear Cell Carcinoma Progression and Immune Regulation

关键词:  肾透明细胞癌  RELT  肿瘤免疫微环境  新型生物标志物

Key words:  Kidney renal clear cell carcinoma  RELT  Tumor immune microenvironment  Novel biomarker

摘要:

目的 肾透明细胞癌（KIRC）是全球范围内普遍存在且死亡率较高的泌尿系统肿瘤。当前，由于缺乏可靠的生物标志物和可行的治疗靶点，KIRC的精准诊断、预后评估与有效治疗仍面临严峻挑战。一种在淋巴组织中表达、并与程序性细胞死亡相关的受体蛋白RELT (Receptor Expressed in Lymphoid Tissues, RELT)，曾被报道与多种癌症生存与预后相关，然其在KIRC中的功能角色仍未明确。综上所述，RELT在KIRC中的诊断潜力、预后相关性及生物学功能亟待探究。方法 本研究从癌症基因组图谱计划 (The Cancer Genome Atlas Project, TCGA) 数据库中获取了多个数据集。采用 Kaplan-Meier 曲线、Cox 回归和 ROC 曲线评估 RELT 的预后意义。使用 ESTIMATE 和 Xcell 算法量化免疫浸润，并通过 GSEA 识别 RELT 调控的通路。对 180 个病理组织样本进行免疫组织化学分析，检测 RELT 蛋白表达及其与生存期的相关性。此外，通过敲除人源肾癌细胞中的RELT 基因，基于 qRT-PCR、蛋白质印迹和 IHC 等生物学实验方法验证其对KIRC的影响。结果RELT 在肿瘤组织中的高表达与 KIRC 患者的不良生存期密切相关。生物信息学和功能实验揭示 RELT 是 KIRC 进展的关键调节因子。RELT 还通过促进 M2 型巨噬细胞、NKT 细胞和 B 细胞的增殖来影响免疫浸润。此外，RELT在小鼠癌细胞凋亡中起关键作用，沉默 RELT 可抑制细胞迁移、侵袭并诱导凋亡。结论RELT 可调节肿瘤免疫微环境，抑制癌细胞生长和转移。它有可能成为 KIRC 的预后生物标志物和新的治疗靶点，为提高KIRC患者生存期提供一种全新的策略。

Abstract:

OBJECTIVE Clear cell renal cell carcinoma (KIRC) is a urinary system tumor that is widespread worldwide and has a relatively high mortality rate. At present, due to the lack of reliable biomarkers and feasible therapeutic targets, the precise diagnosis, prognosis assessment and effective treatment of KIRC still face severe challenges. RELT (Receptor Expressed in Lymphoid Tissues, RELT), a receptor protein expressed in lymphoid tissues and associated with programmed cell death, has been reported to be related to the survival and prognosis of various cancers, but its functional role in KIRC remains unclear. In conclusion, the diagnostic potential, prognostic correlation and biological functions of RELT in KIRC are in urgent need of exploration. METHODS This study obtained multiple datasets from the database of The Cancer Genome Atlas Project (TCGA). The prognostic significance of RELT was evaluated by Kaplan-Meier curve, Cox regression and ROC curve. The ESTIMATE and Xcell algorithms were used to quantify immune infiltration, and the pathways regulated by RELT were identified through GSEA. Immunohistochemical analysis was performed on 180 pathological tissue samples to detect the expression of RELT protein and its correlation with survival period. In addition, by knocking out the RELT gene in human renal cancer cells, the effect on KIRC was verified based on biological experimental methods such as qRT-PCR, Western blotting and IHC. RESULTS The high expression of RELT in tumor tissues is closely related to the poor survival period of patients with KIRC. Bioinformatics and functional experiments have revealed that RELT is a key regulatory factor for the progression of KIRC. RELT also affects immune infiltration by promoting the proliferation of M2-type macrophages, NKT cells and B cells. In addition, RELT plays a key role in the apoptosis of mouse cancer cells. Silencing RELT can inhibit cell migration, invasion and induce apoptosis. CONCLUSION RELT modulates the tumor immune microenvironment and suppresses cancer cell growth and metastasis. It holds promise as a prognostic biomarker for kidney renal clear cell carcinoma (KIRC) and as a novel therapeutic target, offering a new strategy to improve survival outcomes in KIRC patients. KEYWORDS: Kidney renal clear cell carcinoma, RELT, Tumor immune microenvironment, Novel biomarker